DIVERSITY OF CTL EPITOPES AND CHLAMYDIA

我们以前已经发现，能够特异性裂解衣原体感染细胞的细胞毒性T淋巴细胞（CTL）在衣原体感染过程中被激活。沙眼将培养的CTL连续转移到感染的小鼠中提供抗C.沙眼本提案中的实验使用生物化学方法来鉴定引起CTL应答的衣原体抗原。本提案中确定的抗原将使用重组炭疽毒素递送系统测试其在疫苗策略中产生保护性免疫的能力。该项目将继续依赖其他核心和项目。初步的实验也提出了将解决这些抗原在人类感染过程中被识别。 我们设想，这里描述的疫苗策略将被纳入一个多价疫苗，旨在刺激免疫系统的多个武器。开发有效的人类疫苗将减少这些感染的发生率，这些感染是造成世界范围内大量发病率的原因。这些实验不仅将进一步了解CTL在衣原体免疫中的重要性，而且还将更好地了解细胞内空泡病原体的免疫识别。 因为在MHC I类分子上呈递的抗原通常存在于宿主细胞的细胞质中，所以识别出一个逃离液泡区室的抗原亚群以用于在MHC I类分子上呈递给CTL将进一步加深我们对这些非常复杂的宿主细胞-病原体相互作用的理解。所鉴定的这类抗原在其他胞内空泡病原体中也可能具有同源物，包括沙门氏菌、军团菌和分枝杆菌。

We have found previously that cytotoxic T-lymphocytes (CTL) capable of specific lysis of Chlamydia infected cells are primed during infection with C. trachomatis. Adoptive transfer of cultured CTL into an infected mouse affords protection against C. trachomatis. The experiments in this proposal use a biochemical approach to identify Chlamydia antigens which give rise to the response by CTL. The antigens identified in this proposal will be tested for their ability to engender protective immunity in a vaccine strategy using a recombinant anthrax toxin delivery system. This project will continue to rely on other cores and projects. Initial experiments are also proposed that will address which of these antigensare recognized during human infection. We envision that the vaccine strategy described here would be incorporated into a multivalent vaccine designed to stimulate multiple arms of the immune system. Development of an effective human vaccine would reduce the incidence these infections that are responsible for a great deal of worldwide morbidity. These experiments will not only further our understanding of the importance of CTL in immunity against Chlamydia, but also will provide better understanding of immune recognition by intracellular, vacuolar pathogens in general. Because antigens presented on MHC class I molecules generally are found in the cytoplasm of host cells, identification of a subset of antigens which escape the vacuolar compartment to be processed for presentation on MHC class I molecules to CTL will further our understanding of these very complex host cell-pathogen interactions. The class of antigens identified may also have homologues in other intracellular vacuolar pathogens including Salmonella, Legionella, and Mycobacterium.